Medical imaging is a well-established technique in the field of equipments for medical applications. A specific medical imaging technique is based on the analysis of an echo signal that results from the application of ultrasound waves to a patient. This technique can advantageously be implemented with the administration of an ultrasound contrast agent (UCA) to the patient (for example, consisting of a suspension of phospholipid-stabilized gas-filled microvesicles); as the contrast agent acts as an efficient ultrasound reflector, it enhances the visualization of a vascular system within the body part where it is present.
A number of signal-processing methods are known in the art for the specific detection of the echo signal generated by the contrast agent, against the naturally occurring echo signal of the surrounding tissues. These methods all exploit, in some way or another, the particular, primarily nonlinear, modes in which contrast agent responds to ultrasound waves (in contrast with the primarily linear scattering by tissues).
Targeted contrast agents have also been proposed in the last years for facilitating the detection of specific pathologies. These contrast agents are formulated in such a way as to bind preferably to specific targets; for example, the desired behavior is achieved by means of a targeting ligand (incorporated in the contrast agent) that binds to a specific receptor on tumoral tissues. In this way, detection of the immobilized contrast agent allows distinguishing pathologies that would be otherwise difficult to identify.
A possible problem associated with the above-mentioned technique is that only a relatively small fraction of the total amount of administered contrast agent actually reaches its target; conversely, most of the contrast agent continues to circulate (for example, until it is filtered in the lungs, in the kidneys and/or in the liver of the patient). Therefore, the echo signal that is measured is the result of different contributions, which are due to the contrast agent immobilized on the target, to the free-flowing (circulating) contrast agent and to the surrounding tissues. However, it is quite difficult to distinguish the echo signal generated by the immobilized contrast agent from the one generated by the circulating contrast agent and the tissues. This adversely affects the spatial delineation and the quantification of the immobilized contrast agent, thereby hindering the correct detection of the pathologies of interest.
Attempts have been made to improve the discrimination of the immobilized contrast agent. For example, “P. A. Dayton, D. Pearson, J. Clark, S. Simon, P. Schumann, R. Zutshi, T. Matsunaga, K. W. Ferrara, Ultrasonic Enhancement of  Expressing-Cells With Targeted Contrast Agents, 2003 IEEE Ultrasonics Symposium”, which is incorporated by reference, proposes a solution that is based on the observation that the echo signal corresponding to the immobilized contrast agent has a narrower bandwidth with respect to the one corresponding to the circulating contrast agent (with the echo signal for the immobilized contrast agent that also has a lower mean frequency and a higher amplitude). The cited document then mentions the possibility of discriminating the different contributions in the echo signal exploiting the large bandwidth that is observed for the circulating contrast agent only (for example, using harmonic imaging strategies).
However, no solution available in the art is completely satisfactory. Therefore, a need is perceived for a technique that would allow detecting the immobilized contrast agent with an acceptable degree of accuracy. Particularly, the problem of efficiently discriminating the immobilized contrast agent from the circulating contrast agent and from the tissues is still unresolved. All of the above hinders the clinical application of the medical imaging techniques based on the targeted contrast agents.
Furthermore, in some instances, it may be desirable to have alternative methods (i.e., different from those known in the art) to distinguish a contrast agent from the surrounding tissues and/or from another (different) contrast agent.